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Background Infectious diseases (ID) physicians are increasingly faced with the challenge of caring for patients with terminal illnesses or incurable infections. Methods This was a retrospective cohort of all patients with an ID consult within an academic health system from 1 January 2014 through 31 December 2023, including community, general, and transplant ID consult services. Results There were 60 820 inpatient ID consults (17 235 community, 29 999 general, and 13 586 transplant) involving 37 848 unique patients. The number of consults increased by 94% and the rate rose from 5.0 to 9.9 consults per 100 inpatients (P <.001). In total, 7.5% of patients receiving an ID consult died during admission and 1006 (2.6%) of patients were discharged to hospice. In-hospital mortality was 5.2% for community ID, 7.8% for general ID, and 10.7% for transplant ID patients (P <.001). Six-month mortality was 9% for all nonobstetric admissions versus 19% for community ID, 20.9% for general ID, and 22.3% for transplant ID. In total 2866 (7.6%) of all patients receiving ID consultation also received palliative care consultation during the same hospitalization. The index ID consult preceded any palliative consult in the majority (69.5%) of cases. A total of 16.3% of patients had a do-not-resuscitate order during the index hospitalization; 12.2% of all patients with a do-not-resuscitate order had this placed on the same day as the ID consult. Conclusions Patients receiving ID consultation were increasingly complex and more likely to die soon after consultation. These results provide a framework for ID clinicians to consider their role in end-of-life care. [ABSTRACT FROM AUTHOR]

Background The ability of antituberculosis drugs to cross the blood–brain barrier and reach the central nervous system is critical to their effectiveness in treating tuberculosis meningitis (TBM). We sought to fill a critical knowledge gap by providing data on the ability of new and repurposed antituberculosis drugs to penetrate into the cerebrospinal fluid (CSF). Methods We conducted a clinical pharmacology study among patients treated for TBM in Tbilisi, Georgia, from January 2019 until January 2020. Serial serum and CSF samples were collected while patients were hospitalized. CSF was collected from routine lumbar punctures with the timing of the lumbar puncture alternating between 2 and 6 hours to capture early and late CSF penetration. Results A total of 17 patients treated for TBM (8 with confirmed disease) were included; all received linezolid, with a subset receiving cycloserine (5), clofazimine (5), delamanid (4), and bedaquiline (2). All CSF measurements of bedaquiline (12), clofazimine (24), and delamanid (19) were below the limit of detection. The median CSF concentrations of cycloserine at 2 and 6 hours were 15.90 and 15.10 µg/mL with adjusted CSF/serum ratios of 0.52 and 0.66. CSF concentrations of linezolid were 0.90 and 3.14 µg/mL at 2 and 6 hours, with adjusted CSF/serum ratios of 0.25 and 0.59, respectively. CSF serum linezolid concentrations were not affected by rifampin coadministration. Conclusions Based on moderate to high CSF penetration, linezolid and cycloserine may be effective drugs for TBM treatment, whereas the utility of bedaquiline, delamanid, and clofazimine is uncertain given their low CSF penetration. [ABSTRACT FROM AUTHOR]

Background It is uncertain whether diabetes affects the risk of developing latent tuberculosis infection (LTBI) following exposure to Mycobacterium tuberculosis (Mtb). We assessed the relationship of diabetes or prediabetes and LTBI among close and household contacts (HHCs) of patients with active pulmonary tuberculosis (TB) disease in Addis Ababa, Ethiopia. Methods In this cross-sectional study, we performed interferon-γ release assays, TB symptom screening, and point-of-care glycolated hemoglobin (HbA1c) testing among HHCs of active TB cases. Diabetes status was classified into diabetes (HbA1c ≥6.5% or self-reported diagnosis), prediabetes (5.7%–6.4%), and euglycemia (≤5.6%). Multivariable logistic regression was used to determine the association of diabetes with LTBI. Results Among 597 study participants, 123 (21%) had dysglycemia including diabetes (n = 31) or prediabetes (n = 92); 423 (71%) participants were diagnosed with LTBI. Twelve of 31 (39%) HHCs with diabetes were previously undiagnosed with diabetes. The prevalence of LTBI among HHCs with diabetes, prediabetes, and euglycemia was 87% (27/31), 73% (67/92), and 69% (329/474), respectively. In multivariable analysis adjusted for age, sex, and HIV status, the odds of LTBI among HHCs with diabetes were 2.33 (95% confidence interval [CI],.76–7.08) times the odds of LTBI without diabetes. When assessing interaction with age, the association of diabetes and LTBI was robust among participants aged ≥40 years (adjusted odds ratio [aOR], 3.68 [95% CI,.77–17.6]) but not those <40 years (aOR, 1.15 [95% CI,.22–6.1]). Conclusions HHCs with diabetes may be more likely to have LTBI than those with euglycemia. Further investigations are needed to assess mechanisms by which diabetes may increase risk of LTBI after Mtb exposure. [ABSTRACT FROM AUTHOR]

Our interviews of inpatient clinicians (physicians, physician assistants) modeled after the Capability, Opportunity, and Motivation Model of Behavior model revealed opportunity and motivation as important drivers for overdiagnosis and overprescribing for asymptomatic bacteriuria in older adults. Understanding these barriers is an important step toward implementing age-friendly stewardship interventions., Competing Interests: Dr Advani reports support from National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases (grant no. K12DK100024), the Centers for Disease Control and Prevention (grant nos. 5U54CK000616-02 and SHEPheRD 75D30121D12733-D5-E003), the Society for Healthcare Epidemiology of America, and the Duke Claude D. Pepper Older Americans Independence Center (National Institute on Aging grant no. P30AG028716), as well as consulting fees from Locus Biosciences (ended), Sysmex America (ended), GlaxoSmithKline, bioMérieux, and the Infectious Diseases Society of America. Dr. Advani became an employee of GSK/ViiV Healthcare after submission and acceptance of this manuscript., (© The Author(s) 2024.)

Objectives: Our study aimed to assess the time to positivity (TTP) of clinically significant blood cultures in critically ill children admitted to the PICU., Design: Retrospective review of positive blood cultures in patients admitted or transferred to the PICU., Setting: Large tertiary-care medical center with over 90 PICU beds., Patients: Patients 0-20 years old with bacteremia admitted or transferred to the PICU., Interventions: None., Measurements and Main Results: The primary endpoint was the TTP, defined as time from blood culture draw to initial Gram stain result. Secondary endpoints included percentage of cultures reported by elapsed time, as well as the impact of pathogen and host immune status on TTP. Host immune status was classified as previously healthy, standard risk, or immunocompromised. Linear regression for TTP was performed to account for age, blood volume, and Gram stain. Among 164 episodes of clinically significant bacteremia, the median TTP was 13.3 hours (interquartile range, 10.7-16.8 hr). Enterobacterales, Staphylococcus aureus, Streptococcus agalactiae, and Streptococcus pneumoniae were most commonly identified. By 12, 24, 36, and 48 hours, 37%, 89%, 95%, and 97% of positive cultures had resulted positive, respectively. Median TTP stratified by host immune status was 13.2 hours for previously healthy patients, 14.0 hours for those considered standard risk, and 10.6 hours for immunocompromised patients (p = 0.001). Median TTP was found to be independent of blood volume. No difference was seen in TTP for Gram-negative vs. Gram-positive organisms (12.2 vs. 13.9 hr; p = 0.2)., Conclusions: Among critically ill children, 95% of clinically significant blood cultures had an initial positive result within 36 hours, regardless of host immune status. Need for antimicrobial therapy should be frequently reassessed and implementation of a shorter duration of empiric antibiotics should be considered in patients with low suspicion for infection., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Much of the high mortality in tuberculosis meningitis (TBM) is attributable to excessive inflammation, making it imperative to identify targets for host-directed therapies that reduce pathologic inflammation and mortality. In this study, we investigate how cytokines and metabolites in the cerebral spinal fluid (CSF) associate with TBM at diagnosis and during TBM treatment. At diagnosis, TBM patients (n = 17) demonstrate significant increases of cytokines and chemokines that promote inflammation and cell migration including IL-17A, IL-2, TNFα, IFNγ, and IL-1β versus asymptomatic controls without known central nervous system pathology (n = 20). Inflammatory immune signaling had a strong positive correlation with immunomodulatory metabolites including kynurenine, lactic acid, and carnitine and strong negative correlations with tryptophan and itaconate. Inflammatory immunometabolic networks were only partially reversed with two months of effective TBM treatment and remained significantly different compared to CSF from controls. Together, these data highlight a critical role for host metabolism in regulating the inflammatory response to TBM and indicate the timeline for restoration of immune homeostasis in the CSF is prolonged., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Much of the high mortality in tuberculosis meningitis (TBM) is attributable to excessive inflammation, making it imperative to identify targets for host-directed therapies that reduce pathologic inflammation and mortality. In this study, we investigate how cytokines and metabolites in the cerebral spinal fluid (CSF) associate with TBM at diagnosis and during TBM treatment. At diagnosis, TBM patients demonstrate significant increases versus controls of cytokines and chemokines that promote inflammation and cell migration including IL-17A, IL-2, TNFα, IFNγ, and IL-1β. Inflammatory immune signaling was strongly correlated with immunomodulatory metabolites including kynurenine, lactic acid, carnitine, tryptophan, and itaconate. Inflammatory immunometabolic networks were only partially reversed with two months of effective TBM treatment and remained significantly different versus control CSF. Together, these data highlight a critical role for host metabolism in regulating the inflammatory response to TBM and indicate the timeline for restoration of immune homeostasis in the CSF is prolonged.